Methadone for Pain Management in Cardiac Surgery

Overseen By Anesthesia Clinical Research Unit

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must not be taking: Opioids

Disqualifiers: Chronic pain, Opioid use disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores methadone's effectiveness in managing pain after heart surgery. Researchers aim to determine whether taking methadone orally before surgery or via IV during anesthesia affects pain relief afterward. The trial includes individuals undergoing planned heart surgery, excluding those with chronic pain already treated with opioids or certain conditions like severe kidney disease. As a Phase 4 trial, this research seeks to understand how this FDA-approved and effective treatment can benefit more patients.

Do I need to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you have chronic pain requiring opioid medications or are on medication-assisted treatment for opioid use disorder, you cannot participate.

What is the safety track record for methadone?

Research has shown that methadone is usually safe for patients undergoing heart surgery. Its use during surgery has been linked to better pain control without major side effects. One study found that methadone reduced pain by 30 to 40% after surgery, with patients reporting well-managed pain. These findings suggest methadone can be a safe choice for managing pain during and after heart surgery. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard pain management options for cardiac surgery, which often include opioids like morphine or fentanyl, methadone offers a unique advantage. Methadone is not only an effective pain reliever but also has a longer duration of action, which could mean fewer doses are necessary, potentially reducing the risk of addiction and side effects associated with higher opioid use. Additionally, researchers are exploring both oral and intravenous administration of methadone, which might offer more flexibility and efficiency in managing post-surgical pain. This dual approach could provide tailored pain management, enhancing recovery experiences for patients.

What is the effectiveness track record for methadone in managing postoperative pain for cardiac surgery?

Research has shown that methadone can help manage pain after surgery. In this trial, participants will receive either oral methadone immediately before transport or intravenous methadone. Studies have found that taking methadone by mouth before surgery can lower pain levels and reduce the need for other pain medications afterward. As a result, patients might require fewer painkillers and experience fewer side effects. Administering methadone through an IV during surgery has also proven effective for pain management in heart surgery. Both methods aim to make recovery more comfortable by better controlling pain. Methadone's approval for pain treatment supports its effectiveness. ^{5 6 7 8 9}

Who Is on the Research Team?

Krishnan Ramanujan

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for patients scheduled for elective cardiac surgery who need pain management. Specific eligibility criteria are not provided, but typically participants must be adults in stable condition without conflicting health issues or medications that could interfere with the study.

Inclusion Criteria

I am scheduled for heart surgery first thing in the morning.

Exclusion Criteria

Opioid use disorder on medication assistance treatment

Prolonged QTc > 500ms

Intolerance to methadone

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Preoperative Treatment

Participants receive oral methadone immediately prior to transport for surgery

Immediate

Intraoperative Treatment

Participants receive intravenous methadone upon induction of general anesthesia

During surgery

Postoperative Monitoring

Participants' pain scores are monitored at various intervals after extubation

72 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methadone

Trial Overview The study aims to compare two ways of managing pain: taking methadone by mouth before being moved for surgery versus getting it through a vein when general anesthesia starts. The goal is to see which method better controls postoperative pain.

How Is the Trial Designed?

Group I: Oral methadone, immediately prior to transport Experimental Treatment 1 Intervention

Group II: Intravenous methadone Active Control 1 Intervention

Methadone is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Dolophine for:

• Pain management
• Opioid use disorder

Approved in European Union as Methadose for:

• Pain management
• Opioid dependence

Approved in Canada as Physeptone for:

• Pain management
• Opioid use disorder

Approved in Japan as Heptadon for:

• Pain management

Approved in Switzerland as Heptanon for:

• Pain management
• Opioid dependence

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Intravenous methadone has been shown to provide effective postoperative pain relief and reduce the need for other opioids, with a similar safety profile to other opioid analgesics, based on a review of multiple studies.

While there is promising evidence for the use of intravenous methadone in managing chronic cancer pain, more research is needed to fully understand its efficacy in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. Mercadante, S.[2023]

A study of 39 patients undergoing opioid rotation from methadone to alternative opioids found that the mean dose ratio for oral methadone to oral morphine equivalent daily dose was 1:4.7, and for intravenous methadone, it was 1:13.5, indicating significant differences in potency between the two forms.

The research suggests that these new dose ratios can help clinicians switch patients to alternative opioids more safely, especially when managing side effects or inadequate pain control from methadone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching from methadone to a different opioid: what is the equianalgesic dose ratio? Walker, PW., Palla, S., Pei, BL., et al.[2018]

Methadone is a unique opioid that not only acts on mu receptors but also has effects on delta receptors and NMDA receptors, making it a complex option for pain management, especially in cases of uncontrolled pain or when other opioids cause toxicity.

While methadone can be safer at lower doses, there are significant risks associated with high doses, including prolonged QT interval and potential for serious heart issues, highlighting the need for more research through randomized controlled trials to better understand its safety and efficacy compared to other opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methadone for treatment of cancer pain. Bryson, J., Tamber, A., Seccareccia, D., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8730623/

Preoperative oral methadone for postoperative pain in ... This pilot study investigated the effect of preoperative oral methadone on pain scores, analgesia requirements, and opioid-induced side effects.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1526590020300444

Methadone in Pain Management: A Systematic Review The purpose of this article is to provide a narrative review of all available randomized controlled trials (RCTs) investigating the effectiveness of methadone ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06720415

Oral and Intravenous Methadone for Analgesia in Cardiac ... The purpose of this study is to compare the effects of administration of oral methadone preoperatively and intravenous methadone upon induction of general ...

4. associationofanaesthetists-publications.onlinelibrary.wiley.com associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/10.1111/anae.16754

Intravenous methadone for pain management in cardiac surgery Introduction Postoperative pain after cardiac surgery remains significant despite the administration of opioids. Methadone may improve pain ...

5. cts.springeropen.com cts.springeropen.com/articles/10.1186/s43057-024-00127-z

The influence of preoperative or intraoperative methadone on ... Methadone may be effective at reducing perioperative pain scores and opioid requirements postoperatively, including at discharge.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10978480/

The role of methadone in cardiac surgery for management ... Intraoperative administration of methadone was associated with better pain control without significant side-effects after cardiac surgery.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07221617

NCT07221617 | Oral Methadone in Cardiac Surgery Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0022522323000892

Pain management and opioid stewardship in adult cardiac ... This document provides core principles, comprehensive strategies, and graded recommendations regarding pain management and opioid stewardship in adult cardiac ...

9. apsf.org apsf.org/article/use-of-methadone-in-the-perioperative-period/

Use of Methadone in the Perioperative Period In addition, pain scores were decreased by 30 to 40% and patient-perceived quality of pain management was significantly improved during POD 1–3 in the methadone ...